Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized mouse, rat, rabbit, dog, baboon and monkey were used as animal model for experimental heat stroke. However, anesthetized mammals models have some limitations, such as neuroprotective effect of anesthetic agents, possible disturbance on injury and recovery of stroke animals by anesthetic agents, difficulty of discussing animal behavior before and after heat stroke, it was also difficult for the models to evaluate cognitive function of animal under hot environment. Considering humanitarian, only awaked and unrestrained mouse heat stroke model was accepted so far. Therefore, we also developed an awaked and unrestrained rat heat stroke model, and found it was helpful to evaluate drug effectiveness for animal behavior and cognitive function under hot environment.